Herpes Zoster

Varicella-zoster virus (VZV) is the agent causing varicella, otherwise known as chickenpox, the common childhood infection. Following resolution of chickenpox, VZV lies dormant in the spinal dorsal root ganglia until a decrease in cellular immunity triggers the reactivation of the virus, resulting in herpes zoster, otherwise known as shingles. 

Shingles is a syndrome characterized by a painful, vesicular rash that is usually restricted to a unilateral dermatomal distribution. At times, especially in the immunosuppressed patient, the infection may spread and produce severe systemic illness, with involvement of multiple visceral organs and multiple dermatomes (disseminated zoster). 

Shingles usually has a benign course, but complications may occur, ranging from mild to life threatening. In properly selected patients, early treatment with antivirals and corticosteroids has been shown to decrease the duration of symptoms and to possibly prevent or ameliorate some complications. 

The clinical manifestations of herpes zoster can be divided into the preeruptive phase (preherpetic neuralgia), acute eruptive phase, and chronic phase (postherpetic neuralgia).

VZV reactivation causes inflammation in the dorsal root ganglion, accompanied by hemorrhagic necrosis of nerve cells. The result is neuronal loss and fibrosis. The distribution of the rash corresponds to the sensory fields of the infected neurons within a specific ganglion. The anatomic location of the involved dermatome often determines the specific manifestations (eg, herpes zoster ophthalmicus [HZO], causing ocular complications, when the trigeminal ganglion is involved).

Pathophysiology-

Central nervous system involvement

While zoster is classically described in sensory (dorsal root) ganglia, it can spread to affect any portion of the nervous system.

Involvement of the anterior horn cells can produce muscular weakness, cranial nerve palsies, diaphragmatic paralysis, neurogenic bladder, and colon pseudo-obstruction.

Wider involvement of the spinal cord can produce Guillain-Barré syndrome, transverse myelitis, and myositis.

In severely ill or immunocompromised patients, general central nervous system (CNS) involvement can be observed in the form of meningoencephalitis or encephalitis. Such presentations are indistinguishable from other forms of meningoencephalitis, although other evidence of acute zoster usually is present.Cerebrospinal fluid (CSF) studies frequently reveal pleocytosis without elevated protein. These infections can be life threatening.

Herpes zoster ophthalmicus

This is potentially the most devastating form of acute zoster.

Herpes zoster ophthalmicus (HZO) results from the reactivation of varicella-zoster virus (VZV) in the trigeminal (fifth cranial) nerve. Any branch of the nerve may be affected, although the frontal branch within the first division of the trigeminal nerve is most commonly involved. This branch innervates nearly all of the ocular and periocular structures.

Ramsay Hunt syndrome

Also known as herpes zoster oticus, geniculate neuralgia, or herpes zoster auricularis, Ramsay-Hunt syndrome is caused by VZV reactivation involving the facial and auditory nerves. 

Vesicular eruptions may manifest on the pinna, tragus, or tympanic membrane or in the auditory canal, as well as anywhere in the facial nerve distribution.

The patient may experience hearing impairment, nystagmus, vertigo, or facial nerve palsy (mimicking Bell palsy).Patients may lose taste sensation in the anterior two thirds of the tongue.

Ramsay Hunt syndrome may go unnoticed and be difficult to diagnose, especially in elderly patients.

Etiology-

VZV is an enveloped, double-stranded deoxyribonucleic acid (DNA) virus belonging to the Herpesviridae family. In humans, primary infection with VZV occurs when the virus comes into contact with the mucosa of the respiratory tract or conjunctiva. From these sites, it is distributed throughout the body via mononuclear cells in the blood stream. In tissue, VZV spreads from cell to cell via direct contact to produce its effects.

After primary infection, the virus migrates along sensory nerve fibers to the satellite cells of dorsal root ganglia where it becomes dormant. This dormancy may be permanent, or the virus may become reactivated by conditions of decreased cellular immunity, resulting in herpes zoster.

Exactly why VZV reactivates from latency is not fully understood. However, cell-mediated, VZV-specific immunity has been shown to be a major factor in determining reactivation of VZV. Cell-mediated, VZV-specific immunity decreases with age and in patients with certain malignancies. These groups have much higher rates of herpes zoster. Patients with hypogammaglobulinemia (a defect of humoral, but not cellular, immunity) do not have a higher rate of zoster. This supports the concept of an important role for cell-mediated immunity in the pathogenesis of VZV infection.

No identifiable environmental, genetic, or social risk factors exist for the development of the reactivation of VZV.

Clinical Features-

Prodromal pain precedes the rash in approximately 70-80% of patients; it is typically confined to the same dermatomal distribution as the rash. In immunocompetent patients, herpes zoster is generally restricted to one dermatome, with possible limited involvement of adjacent dermatomes due to normal variations in innervation. Many patients describe the pain as "burning," "throbbing," or "stabbing." It may be severe, mild, constant, rare, or felt as another sensation such as pruritus. The involved area may be tender to palpation.

After 48-72 hours, or longer in some cases, the rash develops. Initially, and briefly, maculopapular lesions rapidly transition to vesicles in 1-2 days. New vesicles tend to form over 3-5 days, sometimes coalescing to form bullae. The lesions then rupture and release their contents, ulcerate, crust over, and dry, over 7-10 days. As with chickenpox, once crusting occurs, the lesions are no longer infectious.

Depending on the dermatome involved, additional physical examination findings may include the following:

• Corneal ulcers, conjunctivitis
• Regional lymphadenopathy
• Cranial nerve palsies
• Peripheral facial nerve palsy
• Delirium, confusion, coma (in patients with meningoencephalitis)
• Loss of taste in the anterior tongue (in Ramsay Hunt Syndrome)

Symptomatic involvement of multiple dermatomes or bilateral aspects of the same dermatome (ie, crossing the midline) may indicate disseminated disease or another etiology such as herpes simplex virus (HSV) infection.

Symptoms and lesions tend to resolve over 10-15 days. However, lesions may require up to 1 month to completely heal. Scarring and hyperpigmentation or hypopigmentation at lesion sites may persist for a long period or may be permanent. Pain duration is variable but is usually less than 1 month. Pain lasting longer than 1 month is referred to, by definition, as postherpetic neuralgia.

Less than 20% of patients have systemic symptoms, such as headache, fever, malaise, or fatigue, at any point during a case of herpes zoster.

Herpes zoster may develop without the typical rash, as aseptic meningitis or zoster sine herpete, which is a condition defined as pain and paresthesias along a dermatome without the development of visible cutaneous involvement

Treatment-

Episodes of herpes zoster are generally self-limited and resolve without intervention. However, effective treatments do exist and can reduce the extent and duration of symptoms, and possibly the risk of chronic sequelae (ie, postherpetic neuralgia) as well. Treatment is of most benefit in those patient populations at risk for prolonged or severe symptoms, specifically, immunocompromised people and persons older than 50 years. The benefit of treating younger and healthier populations is unclear.

Uncomplicated zoster does not require inpatient care. Patients at high risk for disseminated zoster may benefit from intravenous (IV) acyclovir. Patients with disseminated zoster usually require admission for IV acyclovir. Inpatient care is also recommended for any patient demonstrating disseminated disease or ophthalmic or meningoencephalopathic involvement.

The use of steroids in conjunction with an antiviral for uncomplicated herpes zoster is controversial.

The addition of oral corticosteroids has been evaluated in patients treated with acyclovir in 2 controlled studies. Steroids were found to accelerate the resolution of acute neuritis and provide a clear improvement in quality-of-life measures in comparison to those patients treated with antivirals alone. The use of oral steroids had no effect on the development or duration of postherpetic neuralgia. Oral steroids have not been studied with valacyclovir or famciclovir, so the benefit is unknown.

Nonoral forms of adjunctive steroid therapy in acute herpes zoster have also been studied. A study involving a single epidural injection of steroids and local anesthetics given in conjunction with a standard regimen of oral antivirals and analgesics was found to modestly improve zoster-associated pain for 1 month over treatment without steroids. As above, no effect in preventing postherpetic neuralgia was noted.

In light of the potential adverse effects of and contraindications to corticosteroid use, current expert opinion suggests limiting their involvement to cases of moderate to severe zoster pain, or in which significant neurological symptoms (such as facial paralysis) or CNS involvement is present (and use of corticosteroids is not otherwise contraindicated).

The optimal duration of steroid therapy is not known. If prescribed, it seems reasonable for steroids to be used concurrently with antiviral therapy. The duration of steroid use should not extend beyond the period of antiviral therapy. Steroids should not be given alone (without antiviral therapy), owing to concern about the promotion of viral replication.

Treatment of complicated herpes zoster-

Individuals with altered cell-mediated immunity, due to an immunosuppressive condition (eg, HIV, cancer) or treatment (eg, extended corticosteroid use), are at increased risk for herpes zoster. Further, herpes zoster presentations in the immunocompromised population can be complicated by disseminated disease and visceral organ involvement.

Antiviral therapy has been demonstrated to halt progression and dissemination of acute herpes zoster in immunocompromised patients, even when initiated more than 72 hours after rash onset.As such, current expert opinion recommends the use of antiviral therapy in all immunocompromised zoster patients who present prior to full crusting of all lesions.

Intravenous acyclovir remains the drug of choice for selected populations of immunocompromised patients, as follows:

• Patients with evidence of disseminated disease or visceral organ involvement
• Patients with ophthalmic involvement
• Patients with advanced HIV/AIDS with active opportunistic infections or prominent wasting
• Transplant recipients soon after transplantation or when being treated for rejection

Patients without such risk factors can be treated with oral antivirals. Data on adjunctive therapy with corticosteroids are lacking, and this therapy is not currently recommended. Antiviral therapy should be continued until resolution of all lesions.